Zoledronic Acid Inhibits Lipopolysaccharide-Induced Osteoclastogenesis by Suppressing Macrophage NLRP3-Mediated Autophagy PathwayDear Editor,The immunomodulatory effects of antiresorptives, particularly nitrogen-containing bisphosphonates (N-BPs), are often overlooked when evaluating their impact on bone health. This critical aspect of N-BP pharmacology warrants greater attention, as it may play a role beyond inhibiting bone resorption—especially in bone conditions where infection and inflammation are significant contributing factors.(1)The recent study by Yuting Cheng et al. provides valuable insights by demonstrating that low concentrations of zoledronic acid exert anti-inflammatory effects, reducing autophagy in macrophages through suppression of the NLRP3 pathway and downregulation of IL-1β levels.(2) While these findings are compelling, the study would greatly benefit from clarification regarding the clinical relevance of the zoledronic acid doses used in their in vitro and animal models. Specifically, indicating whether such low concentrations could be the norm in patients receiving intravenous or oral bisphosphonate preparations would enhance the translational significance of their results and provide valuable clinical context.

javascript:void(0) Tumor patients take a high risk of SARS-CoV-2 infection, high incidence of serious events, poor prognosis and high mortality in the coronavirus disease 2019 (COVID-19) epidemic, but there is still lack of supporting evidence that the COVID-19 vaccination is beneficial for tumor patients to encourage them to receive the vaccination. A cross-sectional study was conducted in Shantou, China and questionnaires were collected in the hospitals from February 13,2023 to April 23,2023. Using the receiving of COVID-19 vaccination as the primary outcome, descriptive, univariate and multivariate analyses were generated.161 out of 241 patients (66.80%) had received at least one dose of COVID-19 vaccine and 61.00% patients had been infected with SARS-CoV-2. Patients with general symptoms (P = 0.013) and others (P = 0.022) had a higher proportion of non-vaccinated patients than vaccinated ones. In the multivariate analysis, age (aOR = 0.971, 95% CI 0.946-0.997, P = 0.031), the cognition of vaccines’ impact on tumor treatment (aOR = 4.475, 95% CI 1.772-11.299, P = 0.002), time since tumor diagnosis (aOR=4.586, 95% CI 2.122-9.909, P < 0.001) were identified as factors of COVID-19 vaccination uptake. COVID-19 vaccination in China brings many benefits to tumor patients, which could reduce symptoms after infection.

Background: Periostin mediates inflammation and fibrosis by regulating ECM adhesion, migration, and differentiation in multiple organ diseases. Studies have shown Periostin mainly located in the dilated mesangium, tubulointerstitial and fibrotic regions of the diabetic nephropathy, which is negatively correlated with renal function. However, the underlying mechanisms remain poorly explored. Methods: The expression of periostin in HK-2 cells was investigated under high glucose and high concentration of TGF-β1. The signaling pathway of periostin involved in epithelial-mesenchymal transdifferentiation of HK-2 cells was also validated. The expression of periostin were investigated by RT-PCR with different concentration of glucose and TGF-β1. Periostin expression in HK-2 cells stimulated by high glucose and high TGF-β1 was detected by western blotting and immunofluorescence. The expression of E-Cad, α-SMA and p38 proteins were also detected. The effects of p38 inhibitors on periostin, E-Cad and α-SMA in high glucose environment were also investigated and verified. Results: High concentration of glucose and TGF-β1 increased the fibrosis of HK-2 cells, prompting high expression of periostin. The combined stimulation of high glucose (22 mmol/L) and high TGF-β1(10 ng/mL) upregulated the expression of periostin obviously, stimulating the expression of α-SMA and p38 while inhibiting the secretion of E-Cad. More importantly, p38 inhibitors reduced the expression of periostin and α-SMA protein while promoted E-Cad protein expression in HK-2 cells under high glucose conditions. Furthermore, p38-MAPK signal pathway was involved in the epithelial-mesenchymal transition of human renal tubules in high glucose environment. Conclusion: Periostin, a downstream factor of TGF-β1, is positively regulated by TGF-β1 under high glucose condition, affecting the epithelial-interstitial differentiation of HK-2 cells via the p38-MAPK signaling pathway. Therefore, periostin may serve as a biomarker of renal fibrosis in diabetic kidney disease.

not-yet-known not-yet-known not-yet-known unknown Introduction: Understand the drug-resistant situation and trend of tuberculosis patients in Yuexiu District, Guangzhou City, from 2013 to 2022, provide a scientific basis for development of rational drug-resistant tuberculosis prevention and control strategies. Methods: All patients who were diagnosed with active tuberculosis in Guangzhou Chest Hospital from January 1, 2013 to December 31, 2022 were collected as study subjects, a total of 5,191 patients were enrolled in the study. The basic conditions and diagnostic and therapeutic information of the study subjects were collected. Sputum specimens were subjected to smear and isolation and culture. Culture-positive strains of bacteria were identified by bacterial groups. A total of 1,659 strains of Mycobacterium tuberculosis (MTB) isolates were obtained. The drug susceptibility test was used the proportionality method on the MTB isolates for nine types of anti-tuberculosis medicines,and comparatively analyzed the resistance of the strains. Results: A total of 1,659 patients with MTB were cultured, 439 were drug-resistant, 255 were mono-resistant, and 121 were poly-resistant, 62 were multidrug-resistant. The resistance rate was 26.46% (439/1659), the mono-resistance rate was 15.37 % (255/1659), and the poly-resistance rate was 7.29% (121/1659), the multidrug resistance rate was 3.74 % (62/1659) . The number (rate) of drug-resistant patients in the primary treatment was 389 [(25.63%).(389/1659）].The number (rate)of drug-resistant patients in retreatment was 50[ (35.46%) (50/1659）]. The number (rate) of multidrug-resistant patients in the primary treatment was 39 (2.57%)[(39/1659）]. The number (rate) of multidrug-resistant cases in retreatment patients was 23 [(16.31%)(23/1659）]. The resistance rate and multidrug resistance rate of isolates from retreatment patients were higher than those of isolates from primary treatment patients, and the differences were statistically significant. Conclusions: The problem of drug-resistant tuberculosis transmission in Guangzhou needs to be focused on, and drug-resistant screening should be further increased to do a good job of controlling the source of infection.

Chronic spontaneous urticaria (CSU) is a debilitating inflammatory skin disease with a prevalence of approximately 1% of the population. It is characterised by recurrent itchy wheals and/or angioedema for more than 6 weeks without known triggers leading to a high quality of life impairment. The pathogenesis of CSU remains not fully understood. This study aimed to explore the pathomechanism of CSU beyond mast cells and IgE-dependent histamine release and to identify possible biomarkers for the disease and its treatment. We investigated a patient cohort in the first month of omalizumab treatment regarding the IgE levels and changes of gene and miRNA expression in peripheral blood. The cohort was divided into responders and non-responders (depending on the score of the Urticaria Control Test) and compared to a group of healthy controls. Our messenger RNA and microRNA microarray analyses revealed the greatest changes of expression levels at day 2 after the first omalizumab dose. We identified several genes and miRNAs of interest, most of which have not been described to be linked to CSU so far, underlining, for example, to T cell involvement or even suggesting platelet involvement.

Objective: This study aims to enhance the management of Epstein-Barr Virus (EBV) infections by analyzing the correlation between laboratory indicators and clinical manifestations in children, thereby proposing more precise diagnostic and treatment strategies. Methods: In this retrospective study included 163 pediatric patients with EBV infections treated at the Children’s Hospital of Soochow University from December 2017 to December 2019. Data collected through retrospective analysis included gender, age, clinical symptoms, signs, liver function tests, T-cell subset distribution, EBV-DNA copy numbers in plasma and whole blood, and treatment outcomes. Patients were grouped based on EBV copy numbers and hospital stay duration to compare clinical indicators across different groups. Results: The dichotomous results of EBV plasma level showed that the two groups of children were significantly different in the number of days of fever (p= 0.0373), platelet count (p= 0.018), ALT (p= 0.0299), immunoglobulin IgM (p= 0.0323), IgG (p= 0.0299), TBiL (p= 0.0037), LDH (p< 0.001), number of CD19+ cells (p= 0.0204) and length of hospital stay (p< 0.001) were significantly different, indicating that EBV plasma levels may be correlated with these characteristic variables.The dichotomous results of the length of hospital stay showed that the two groups were significantly increased in tonsil enlargement (p= 0.0024), platelet count (p= 0.00449), LDH (p= 0.0394), CD3+ cell count (p= 0.0383), and ferritin (p= 0.0106) and EBV plasma levels (p< 0.001) were significantly different, This suggests a potential correlation between EBV plasma levels and these clinical indicators. Conclusion: Variations in platelet counts and lactate dehydrogenase (LDH) levels in children with EBV infections may serve as indicators of clinical outcomes.

Background: Efficacy of allergen immunotherapy is dose-dependent; however, high doses of allergen may imply a greater risk of adverse reactions. Objective: To assess the safety and tolerability of subcutaneous immunotherapy (SCIT) with mixtures of mite allergen extracts, Dermatophagoides pteronyssinus/Blomia tropicalis (Dpt/Bt) and Dermatophagoides pteronyssinus/Lepidoglyphus destructor (Dpt/Ld) at maximum concentrations, in adult patients with allergic rhinitis or rhinoconjunctivitis, and controlled allergic asthma due to a clinically relevant sensitisation to these mites. Methods: An open-label, non-controlled, non-randomised, phase IIb clinical trial was carried out in three hospitals in Spain between September 2014 and May 2018. Patients received SCIT of either Dpt/Bt (100/1000 DPP/mL) or Dpt/Ld (100/100 DPP/mL) in two phases: a rush build-up phase on the first day (0.2 mL and 0.3 mL with a 30-minute interval) and a monthly maintenance phase administration (0.5 mL) up to 48 months. Results: Forty patients were recruited for the study, seven allocated to the Dpt/Bt group and 33 to the Dpt/Ld. None experienced immediate or delayed systemic Grade ≥2 reactions (EAACI classification) (systemic reactions were mostly Grade 1) nor died during the study. Local reactions were mostly mild (0‒10 cm). Thirty-nine patients (97.5%) experienced at least one adverse event (AE). Of the 283 reported AEs, eight (2.8%) were systemic reactions experienced by six (15%) subjects and 14 (4.9%) were local reactions sustained by ten (25%) subjects. Conclusions: SCIT treatment of patients with allergic rhinitis or rhinoconjunctivitis and controlled asthma with mixtures of Dpt/Bt and Dpt/Ld allergen extracts at maximum concentrations showed a favourable safety profile. Keywords: allergic asthma, allergic rhinitis, Blomia tropicalis, Dermatophagoides pteronyssinus, House dust mites, Lepidoglyphus destructor, maximum extract concentrations. safety,

Objective: This study aims to investigate the correlation between changes in Bone Mineral Density (BMD) in postmenopausal women and circulating inflammatory markers. Methods: This retrospective study focused on postmenopausal women admitted to the orthopedic department of Suzhou Benq Medical Center from June 2022 to December 2023, following predetermined inclusion and exclusion criteria. We retrospectively collected data on initial blood routine test results and bone density measurements for all study subjects upon admission, including parameters such as White Blood Cell count (WBC), C-reactive protein (CRP), Interleukin-6 (IL-6), and Procalcitonin (PCT). Additionally, the Systemic Immune-inflammation Index (SII) was calculated using Neutrophil Count, Lymphocyte Count, and Platelet Count. Statistical analyses using SPSS and GraphPad software were performed to assess the correlation between bone density and inflammatory markers. Results: Patients were classified into three groups based on BMD results, including 60 individuals in the Osteoporosis (OP) group, 127 individuals in the Osteopenia (ON) group, and 37 individuals in the Normal (NO) group, respectively. Principal Component Analysis (PCA) analysis suggested that WBC, SII, and PMOP held significant feature values. Correlation analysis indicated a correlation between WBC (P=0.021), IL-6 (P=0.044), SII (P=0.034), and PMOP. One-way ANOVA analysis revealed significant differences in IL-6 (P=0.0179), SII (P=0.0210), and PCT (P=0.0200) among the three groups. Finally, ROC curve analysis demonstrated that SII (area under the curve = 0.716) has predictive value for PMOP. Conclusion: This study identified a certain predictive value for PMOP through the assessment of inflammatory markers in peripheral blood using routine blood tests.

Cerebral ischemic disease is the most common cerebrovascular disease, especially ischemic stroke. Exercise has a protective function on brain tissues following cerebral ischemia-reperfusion injury (CIRI), but its preventive effect and mechanism in CIRI remain unclear. This research aimed to investigate the effect and mechanism of exercise preconditioning on CIRI. The middle cerebral artery occlusion (MCAO) operation was prepared to set up CIRI rats. All rats were randomized into the MCAO, exercise (exercise preconditioning plus MCAO operation), vector (exercise preconditioning, MCAO operation plus intraventricular injection of empty vector), and tissue inhibitor of metalloprotease 1 overexpression (OE-TIMP1) groups (exercise preconditioning, MCAO operation plus intraventricular injection of OE-TIMP1). The results indicated that exercise preconditioning effectively suppressed the brain dysfunction and TIMP1 mRNA level in MCAO rats, which was partially offset by OE-TIMP1. Also, the attenuation of exercise on the neuron death status and the infarction size in MCAO rats was counteracted by OE-TIMP1. This study also confirmed that exercise weakened apoptosis and oxidative stress damage, with a notable increase of Bcl-2, superoxide dismutase, and glutathione peroxidase production, and an evident decrease of Bax, caspase 3, and malondialdehyde in MCAO rats, while the effect was partially reversed after overexpressing TIMP1. Additionally, the down-regulation of exercise on the protein levels of TIMP1, hypoxia-inducible factor-alpha, vascular endothelial growth factor receptor-2, VEGF, and Notch 1 in MCAO rats was partially reversed by OE-TIMP1. Altogether, exercise preconditioning had protective effects on CIRI by restraining TIMP1. This study provides new targets and therapeutic strategies for the prevention of CIRI.

Background: The pathomechanism of blast TBI and blunt TBI is different. In blast injury, evidence indicate that a single blast exposure can often manifest long-term neurological impairments. However, its pathomechanism is still elusive and treatments were symptomatic. Poly ADP Ribose Polymerase-1 (PARP1) is being implicated in the parthanatos and secondary neuroinflammation. Animal studies indicate the over-activation of as a major downstream event underlying the neurological sequalae of several traumatic and neurodegenerative disorders irrespective of the mode of cell death. PARP over-activation forms ADP polymers on several nuclear proteins known as trans-PARylation by consuming NAD+ and ATP. As NAD+ is a substrate for sirtuins, it too has been implicated in the oxidative stress underlying TBI pathology. Hypothesis: We recently established the implication of PARP1 following blast overpressure (BOP) and its differential response on astrocytes and microglial cells. We found that the inhibition of PARP is proven to be beneficial by attenuating oxidative stress. In this study, we hypothesized the involvement of the PARP1-SIRT-NRF2 axis following Blast induced PARP over-activation in glial cells for the manifestation of oxidative stress in BOP insults. Objective: Our objective is to determine the downstream modulation of the PARP-Sirt-NRF2 axis and changes in ATP levels following blast exposure in astrocytes and microglia cell lines. Results: As a result of NAD+ being a common substrate for PARP1 and Sirtuins, we found the decreased expression of SIRT1, SIRT3 and NRF2, a major transcriptional regulator for the expression of antioxidant genes. We found that ATP levels were elevated post-BOP from both glycolysis and oxidative phosphorylation (OXPHOS), an increase of ATP by glycolysis more significant than OXPHOS source indicating the pro-inflammation post-BOP. Conclusion: This result shows that blast-induced PARP over-activation impacts the deacetylation activity of sirtuins and consequently impacts the regulation of antioxidant levels in astrocytes and microglia.

Systemic sclerosis (SSc) is an autoimmune rheumatic disorder distinguished with fibrosis and vascular injury and structural alteration, coexisting with Reynaud’s phenomenon. The crosstalk between activated fibroblasts, immune effectors, and endothelial cells are the primary culprits in disease process. Fractalkine (FKN) or CX3CL1 is an unremarkable membrane-bound soluble chemokine and an adhesion molecule expressed on pro-inflammatory cytokine. In this systematic review, FKN and its receptor’s (CX3CR1) role in mediating inflammatory processes focusing on the pathogenesis of SSc is investigated. FKN is one of the most influential molecules which monitors the trafficking of inflammatory cells through the endothelium and has been observed to have pronounced expression in inflammation. The correlation between increased CX3CL1 levels in SSc and interstitial lung disease was established, and it was noted that CX3CL1 is predominantly co-localized with infiltrating mononuclear cells and epithelia within the lungs. The interstitial lung disease prediction and its progression may be available through augmented concentrations in SSc patients. Conclusively, Emerging evidence claims that FKN could be expressed in numerous tissues, taking part in the CX3CR1 positive cell accumulation at sites of inflammation and, as a result, involved in countless rheumatic diseases such as rheumatoid arthritis, Systemic lupus erythematosus, and scleroderma. Besides, it may play a prominent part in the SSc pathogenesis, involving vascular injury and tissue inflammation. Its estimation could be used as a serological marker for the recognition and follow-up of skin and pulmonary complications.

Enterovirus D68 (EV-D68) has gained attention as a respiratory and neuropathogen, particularly affecting children and causing outbreaks of severe respiratory illness and acute flaccid myelitis. This review explores the current state of knowledge regarding the immunology of EV-D68, delving into the intricate interactions between the virus and the host immune system. From the initial encounter of the virus with the innate immune response to the development of adaptive immunity, we navigate through key aspects of EV-D68 immunology. 1. Innate Immune Response: The journey begins with the recognition of EV-D68 by the innate immune system. Pattern recognition receptors (PRRs) identify viral components, triggering a cascade of antiviral responses. The role of interferons, natural killer cells, and other innate immune effectors in controlling early viral replication is highlighted. 2. Adaptive Immunity: The adaptive immune system orchestrates a more targeted and specific defense against EV-D68. B cells produce antibodies that recognize and neutralize the virus, while T cells play a crucial role in coordinating and regulating the immune response. This section explores the dynamics of antibody-mediated immunity and the cellular immune response in the context of EV-D68 infection. 3. Viral Evasion Mechanisms: EV-D68 employs various strategies to evade the host immune response, including antigenic variation and interference with host antiviral pathways. Understanding these mechanisms is vital for developing effective countermeasures. 4. Vaccine and Therapeutic Developments: A critical aspect of EV-D68 immunology is the ongoing efforts to develop vaccines and antiviral therapies. This section provides an overview of current research and potential strategies for preventing and treating EV-D68 infections. 5. Future Perspectives: The review concludes by highlighting the gaps in our understanding of EV-D68 immunology and proposing avenues for future research. The importance of a comprehensive approach to tackle this evolving respiratory pathogen is emphasized.

摘要： 破骨细胞是骨质疏松症发展不可或缺的一部分 （OP）及其在氧化应激（OS）条件下的产生 涉及多种途径。但是，通过具体机制 天然抗氧化剂山奈酚（KAE）减轻了OS的影响 破骨细胞仍然有些不确定。为了评估 KAE对OS下破骨细胞形成的影响及探讨其可能性 机制。在这项研究中，斑马鱼被用来观察 OP 和 OS 上的 KAE。 OP 和 OS“双重疾病靶点”网络 采用药理学预测KAE的作用靶点及机制 在操作系统下的 OP 上。KAE对破骨细胞分化的影响 使用 LPS 诱导的 RWA264.7 细胞评估 OS。阐明 潜在机制，为了阐明其可能的机制， 诱导过程中相关因子和靶基因的表达量为 检测。结果：KAE的存在显示出改善的潜力 斑马鱼的 OP 和 OS 状况。KAE可以降低RAW的操作系统 264.7 细胞受 LPS 刺激，抑制破骨细胞的形成，以及 改变OS相关因素水平，减少OS增加 陷阱。网络药理学和靶基因表达的利用 分析显示，KAE对 原癌基因酪氨酸蛋白激酶 （SRC） 的表达，核 因子 κ-B （NF-κB）、丝氨酸/苏氨酸激酶-1 （AKT1）、一氧化氮 合酶 3 （NOS3） 和基质金属肽酶-2 （MMP2）。基于这些 研究结果，可以得出结论，KAE可以有效地缓解OS和 通过 SRC/NF-ΚB-AKT/NOS3 阻碍破骨细胞的形成 轴。

Abstract Giant cell arteritis (GCA) is a prevalent vasculitis primarily affecting larger vessels, notably in individuals aged 70–79. Cerebrovascular ischemic events (CIE), such as stroke and transient ischemic attacks, are significant GCA complications, with a pooled prevalence of 4%. CIEs are rare but debilitating complications of GCA. This research article is a narrative review that aims to highlight the risk factors and pharmacological interventions that impact GCA-related CIE. This narrative review suggests that age, male gender, hypertension, and smoking were significantly associated with GCA-related CIE, while risk factors such as having anemia, a higher body mass index (BMI), relatively higher inflammatory markers such as C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) had protective effects against GCA-related CIE. Symptoms of ischemia of the ophthalmic artery were also found to be the strongest predictors of CIE. Pharmacological interventions such as glucocorticoids and tocilizumab can help manage and prevent CIE in GCA patients. Aspirin and antiplatelet therapy may also be useful as adjunctive therapies. A detailed and appropriate study design for various risk factors is required to establish the association. Identifying risk factors is imperative for managing morbidity and mortality. This can help physicians assess the risk and prevent CIE in GCA patients.

Pirfenidone has evinced noteworthy anti-inflammatory and antifibrotic efficacy in both animal models and in some clinical trials. Its pronounced potential for antifibrotic activity makes pirfenidone a compelling prospect for the treatment of various fibrotic diseases. Pirfenidone has several pleiotropic and anti-inflammatory mechanism of action through different molecular pathways. Consequently, it attenuates multiple inflammatory processes, including the secretion of pro-inflammatory cytokines, apoptosis, and fibroblast activation. Extensively studied for idiopathic pulmonary fibrosis, pirfenidone has exhibited a favorable impact, and represents part of the current treatment for this disease. In similar fibrotic diseases such as interstitial lung disease, myocardial fibrosis, glomerulopathies, aberrant skin scarring, chronic liver disease, and other fibrotic disorders, pirfenidone seems to exert a beneficial effect. Given the growing incidence of chronic fibrotic conditions, pirfenidone emerges as a potential therapeutic option for the management of these patients. Nonetheless, more clinical trials are needed to confirm its therapeutic effect. In this review, we aim to expose the current evidence of pirfenidone's effect in several fibrotic diseases.

Radiation proctitis (RP) refers to rectal injury caused by radiation treatment of pelvic and retroperitoneal malignancies, which seriously affects the treatment prognosis and life quality of cancer patients. However, effective medicine for treating RP has not found yet. Ginsenoside Rg3 (GRg3) is a tetracyclic triterpene saponin monomer, which is the main bioactive component of ginseng extract. In this study, we found that GRg3 significantly improved the general condition and histopathological damage on RP rats. In addition, it has been found out that GRg3 decreased the levels of pro-inflammatory factors (TNF-α) and increased the levels of anti-inflammatory factors (IL-4, IL-10). Meanwhile, RT-qPCR and Western blot assays showed that GRg3 significantly inhibited the activation of NF-κB and Caspase-8 signaling pathways. The results suggest that GRg3 may reduce the inflammatory response by inhibiting the NF-κB signaling pathway and improving the balance of inflammation-related factors. GRg3 may also inhibit intestinal cell apoptosis by suppressing the TNF-α/Caspase-8 signaling cascade, thereby reducing radiological rectal injury. Therefore, ginsenoside Rg3 may be a promising therapeutic agent for RP.

Background: For a long time, the prevailing viewpoint suggests that shorter telomere contribute to chromosomal instability, which is a shared characteristic of both aging and cancer. The newest research presented that T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to some cancers. However, the relationship between genetically determined telomere length and immune cells remains unclear. Methods: The two-sample Mendelian randomization (MR) analysis was conducted to elucidate the potential causal relationship. The genetic data of telomere length and the quantity of lymphocytes were obtained from the Genome-Wide Association Study. The inverse variance-weighted method was used to estimate the effects primarily and another four methods were as a supplement. Relevant sensitivity analysis was used to test the results. Results: The IVW method showed a significant correlation between telomere length and the percentage of T lymphocytes (OR: 1.222, 95% CI: 1.014-1.472, P = 0.035), indicating that short telomere length significantly increases the risk of low T cell percentage. Further analysis of T cell subsets indicated that shorter telomere length may primarily lead to a lower proportion of Natural Killer T cells (OR: 1.574, 95% CI: 1.281-1.935, P < 0.001). Analysis of B cell subsets revealed that shorter telomere length may be associated with a higher proportion of Naive-mature B cells, and a lower proportion of Memory B cells. And the sensitivity analysis indicated the validity and robustness of our findings. Conclusion: In summary, a causal relationship existed between telomere length and the quantity and differentiation of immune cells. Specifically, genetically predicted shorter telomere length was found to increase the risk of occurrence of immunosuppression and immunodeficiency.

Objectives:The purpose of this study was to examine the proportion of CD161 on CD56+Natural Killer(NK) cells in peripheral blood of primary Sjögren’s syndrome(pSS) and investigate its clinical relevance of pSS. Methods:The proportion of CD56+NK cells and CD161 on CD56+NK cells was detected by flow cytometry in 31 pSS patients and 29 healthy controls (HCs). The correlations between proportion of CD161+CD56+NK cells and clinical features and disease activity of pSS were further analysed. Meanwhile, we drew the receiver operating characteristic(ROC) curve to evaluate the diagnostic value of CD161+CD56+NK cells in pSS. Results: The proportion of CD56+ NK cells and CD161+CD56+NK cells decreased markly in pSS patients compared to HCs. The correlation analysis showed that proportion of CD161+CD56+NK cells negatively correlated with WBC,IgA,IgM,IgG,ESSRPI and ESSDAI,and positively correlated with complement C4.The proportion of CD161+CD56+NK cells in pSS patients with decayed tooth, fatigue, arthralgia, skin involvement, primary biliary cirrhosis(PBC),interstitial lung disease(ILD), anti-SSA/Ro60 positive, anti-SSB positive and high IgG was lower than that in negative patients. Furthermore, compared with innactive patients,the proportion of CD161+CD56+NK cells decreased obviously in active patients. The area under the curve(AUC)was 0.7375(P=0.0016),the results indicated that CD161+CD56+NK cells had certain diagnostic value for pSS. Conclusion: This study suggested that the proportion of CD56+NK cells and CD161+CD56+NK cells decreased significantly in pSS patients,and the proportion of CD161+CD56+NK cells negatively associated with the clinical features and disease activity of pSS patients. The CD161+CD56+NK cells may present as a potential target for therapy and a biomarker of disease activity in pSS .